Hair Follicle Targeting and Dermal Drug Delivery with Curcumin Drug Nanocrystals-Essential Influence of Excipients.

Olga Pelikh,Cornelia M Keck

doi:10.3390/nano10112323

Abstract

Many active pharmaceutical ingredients (API) possess poor aqueous solubility and thus lead to poor bioavailability upon oral administration and topical application. Nanocrystals have a well-established, universal formulation approach to overcome poor solubility. Various nanocrystal-based products have entered the market for oral application. However, their use in dermal formulations is relatively novel. Previous studies confirmed that nanocrystals are a superior formulation principle to improve the dermal penetration of poorly soluble API. Other studies showed that nanocrystals can also be used to target the hair follicles where they create a drug depot, enabling long acting drug therapy with only one application. Very recent studies show that also the vehicle in which the nanocrystals are incorporated can have a tremendous influence on the pathway of the API and the nanocrystals. In order to elucidate the influence of the excipient in more detail, a systematic study was conducted to investigate the influence of excipients on the penetration efficacy of the formulated API and the pathway of nanocrystals upon dermal application. Results showed that already small quantities of excipients can strongly affect the passive dermal penetration of curcumin and the hair follicle targeting of curcumin nanocrystals. The addition of 2% ethanol promoted hair follicle targeting of nanocrystals and hampered passive diffusion into the stratum corneum of the API, whereas the addition of glycerol hampered hair follicle targeting and promoted passive diffusion. Propylene glycol was found to promote both pathways. In fact, the study proved that formulating nanocrystals to improve the bioefficacy of poorly soluble API upon dermal application is highly effective. However, this is only true, if the correct excipient is selected for the formulation of the vehicle. The study also showed that excipients can be used to allow for a targeted dermal drug delivery, which enables to control if API should be delivered via passive diffusion and/or as drug reservoir by depositing API in the hair follicles.

Highlights

IntroductionTopical drug delivery is a major and constantly growing market in the pharmaceutical field
Besides oral drug delivery, topical drug delivery is a major and constantly growing market in the pharmaceutical field
Results showed that already small quantities of excipients can strongly affect the passive dermal penetration of curcumin and the hair follicle targeting of curcumin nanocrystals

Summary

Introduction

Topical drug delivery is a major and constantly growing market in the pharmaceutical field. The high prevalence of skin diseases or injuries, as well as the increasing demand of topically applied drugs for transdermal drug delivery, require the development of innovative and effective formulations that can overcome current challenges in this field. The therapy concept that combines efficient drug delivery and skin protecting or restoring properties at the same time, is known as advanced corneotherapy and can help to improve the treatment efficacy and compliance of the patients [2]. There is an increasing demand to formulate topical drug products as a depot, i.e., formulations that are applied once and release the active compound over an extended period of time. Most prominent examples for extended dermal drug delivery are transdermal patches that can be worn for several days or microneedle patches where biodegradable drug-loaded microneedles are deposited into the skin where they can act as a long-term reservoir for drugs [3,4,5]

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